Human fetal hemoglobin (HbF) differs from HbA in both functional and structural aspects. These differences are evidenced by the weaker affinity of HbF for 2,3-diphosphoglyceric acid, and by the non-participation of HbF in gel formation with HbS. We are using immunoabsorption with hemoglobin A to isolate nonprecipitating antibodies specific for the gamma chains of hemoglobin F which do not cross react with HbA or other hemoglobins. A radioimmunoassay using reductively methylated 3(H)-hemoglobin F and synthetic peptides from regions of the gamma chains will be used to assess the specificity of binding. The antibodies will be useful in quantitating small amounts of HbF in standard laboratory procedures and in prenatal diagnosis of hemoglobinopathies. Antibodies obtained by similar methods will be used to identify mutant hemoglobins in cell culture. We have also obtained crystals of met-HbF of suitable size for X-ray diffraction studies. The specific antibodies and X-ray studies will give information on the conformational and surface structural characteristics of HbF which are the basis of its immunogenic behavior.